The following discussion of the prior art is intended to present the invention in an appropriate technical context and allow its significance to be properly appreciated. Unless clearly indicated to the contrary, however, reference to any prior art in this specification should be construed as an admission that such art is widely known or forms part of common general knowledge in the field.
Sitagliptin (CAS 486460-32-6) is an oral antihyperglycemic (antidiabetic) drug of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. It was developed, and is marketed, by Merck & Co under the trade name of JANUVIA. The tablets contain sitagliptin phosphate, an orally-active inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme. This enzyme-inhibiting drug is used either alone or in combination with other oral antihyperglycemic agents (such as metformin or a thiazolidinedione) for treatment of diabetes mellitus type 2.
Sitagliptin phosphate monohydrate is chemically named as 7-[(3R)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine phosphate (1:1) monohydrate and has the following structural Formula (I).

U.S. Pat. No. 6,699,871 B2 (the U.S. '871 patent) and J. Med. Chem. 2005, Vol. 48 (1), 141-151 discloses process for preparation of sitagliptin by coupling (3R)—N-(tert-butoxycarbonyl)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid of Formula (V) with 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-a]pyrazine of Formula (IV) or salt thereof under standard peptide coupling conditions by using 1-ethyl-3-(3-dimethylaminopropyl)carbodimide (EDC), 1-hydroxy-benzotriazole (HOBT) and a base diisopropylethylamine in solvents like N,N-dimethylformamide (DMF) or methylene dichloride (MDC).
U.S. Pat. No. 7,326,708 B2 (the U.S. '708 patent) discloses preparation of sitagliptin dihydrogenphosphate salt and crystalline hydrates thereof, in particular a crystalline monohydrate and their pharmaceutical compositions. In particular, the U.S. '708 patent discloses preparation of sitagliptin phosphate salt by using one equivalent of phosphoric acid with respect to sitagliptin from 25° C. to 100° C. in organic solvent or aqueous organic solvent.
U.S. Pat. No. 7,495,123 B2 (the U.S. '123 patent) discloses process for preparation of enantiomerically enriched beta amino acid derivatives i.e. sitagliptin wherein the amino group is unprotected by asymmetric hydrogenation of a prochiral beta amino acrylic acid or derivative thereof, wherein the enamine amino group is unprotected, in the presence of a rhodium metal precursor complexed with a chiral mono- or bisphosphine ligand.
U.S. PG-Pub. No. 2009/0123983 A1 discloses the enzymatic reduction processes for the preparation of (S) or (R) methyl 4-(2,4,5-trifluorophenyl)-3-hydroxybutanoate, an intermediate in the synthesis of sitagliptin by combining methyl 4-(2,4,5-trifluorophenyl)-3-hydroxybutanoate with an enzyme that stereoselectively reduces a ketone to form an alcohol, and co-factor.
U.S. PG-Pub. No. 2009/0192326 A1 (the U.S. '326 A1) discloses a process for preparation of 3-amino-4-(2,4,5-trifluorophenyl)butanoic acid alkyl ester, an intermediate of sitagliptin and process for preparation of sitagliptin. The U.S. '326 A1 discloses reacting 3-tert-butoxycarbonylamino-4-(2,4,5-trifluorophenyl) butanoic acid with 3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine hydrochloride in presence of dicyclohexylcarbodiimide as coupling agent and 4-dimethylaminopyridine (DMAP) as catalyst to obtain 4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)-4-oxobutan-2-yl-carbamate in N,N-dimethylformamide (DMF), and then removing the amino protected group in 4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)-4-oxo butan-2-yl-carbamate to obtain sitagliptin.
International (PCT) Publication WO 2010/122578 A2 discloses process for preparation of sitagliptin by coupling (3R)—N-(tert-butoxycarbonyl)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid of Formula (V) with 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-a]pyrazine hydrochloride of Formula (IV) under standard peptide coupling conditions using suitable condensing agent N,N′-Dicyclohexyl carbodiimide (DCC) in presence of hydroxybenzotriazole (HOBT) or 4-dimethylaminopyridine (DMAP).
International (PCT) Publication WO 2012/150328 A2 discloses alternative processes for the preparation of sitagliptin wherein N,N′-Dicyclohexyl carbodiimide (DCC) or 1-ethyl-3-(3-dimethyl-aminopropyl)carbodimide (EDC) is used as coupling agent in presence of hydroxybenzotriazole (HOBT).
International (PCT) Publication WO 2013/013833 A1 discloses the process for preparation of sitagliptin comprises reaction carried out under standard peptide coupling conditions, using 1-ethyl-3-(3-dimethylaminopropyl)carbodimide (EDC), 1-hydroxybenzotriazole (HOBT) and a base usually diisopropylethyl-amine, in a solvent such as N,N-Dimethylformamide (DMF) or methylene dichloride (MDC). The protecting group is then removed with trifluoroacetic acid or methanolic hydrogen chloride in the case of tert-butoxycarbonyl as protecting group.
Therefore, one of the objectives of the present invention is to provide an alternative approach for the preparation of sitagliptin which avoids use of standard coupling agents and which provides at least a useful alternative approach over the one disclosed in the art. In view of the above cited prior art, it is therefore, desirable to provide an efficient process for the preparation of sitagliptin.